WO2005092291A1 - Prolonged-release compositions comprising torasemide and a matrix-forming polymer - Google Patents

Prolonged-release compositions comprising torasemide and a matrix-forming polymer Download PDF

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Publication number
WO2005092291A1
WO2005092291A1 PCT/EP2005/051340 EP2005051340W WO2005092291A1 WO 2005092291 A1 WO2005092291 A1 WO 2005092291A1 EP 2005051340 W EP2005051340 W EP 2005051340W WO 2005092291 A1 WO2005092291 A1 WO 2005092291A1
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Prior art keywords
prolonged
release compositions
torasemide
compositions according
matrix
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PCT/EP2005/051340
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French (fr)
Inventor
Alfonso Romero
Marta Guerrero
Antonio Guglietta
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Ferrer Internacional, S.A.
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Priority to MXPA06010833A priority Critical patent/MXPA06010833A/en
Priority to KR1020067021596A priority patent/KR101203763B1/en
Priority to CN2005800093895A priority patent/CN1946379B/en
Priority to ES05717133.2T priority patent/ES2632354T3/en
Priority to AU2005227095A priority patent/AU2005227095B2/en
Application filed by Ferrer Internacional, S.A. filed Critical Ferrer Internacional, S.A.
Priority to JP2007504420A priority patent/JP4871258B2/en
Priority to CA2562142A priority patent/CA2562142C/en
Priority to EP05717133.2A priority patent/EP1732517B1/en
Priority to BRPI0509165-9A priority patent/BRPI0509165A/en
Priority to US10/594,004 priority patent/US20080187585A1/en
Publication of WO2005092291A1 publication Critical patent/WO2005092291A1/en
Priority to NO20064834A priority patent/NO336582B1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics

Definitions

  • This invention relates to prolonged-release diuretic compositions containing torasemide as active ingredient.
  • Figure 1 shows the curves of in-vitro release rate (cumulative values) of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8.
  • Figure 2 shows the curves of in-vitro release rate of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8.
  • Figure 3 shows the plasma concentration curves in man after administration of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8.
  • Figure 4 shows the versus-time curves of the number of urinary urgencies in man after administration of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8.
  • Torasemide (US 4018929) is a potent diuretic with an extensive clinical use. Torasemide mainly acts by inhibiting sodium reabsorption in the ascending limb of Henle's loop (Puschett JB and Jordan LL. Mode of action of Torasemide in man. Progress in Pharmacology and Clinical Pharmacology. 1990; 8 (1) : 7-13) . Torasemide interferes with Na + 2C1 " K + pump in the luminal cell membrane and blocks the basolateral chloride conductance (Greger R. Inhibition of active NaCl reabsortion in the thick ascending limb of the loop of Henle by torasemide. Arzneim Forsch . /Drug Res. 1988;38(1) :151-155) .
  • the bioavailability for torasemide is 80-90% after oral administration, the kinetics is linear and the elimination half-life is 3-4 hours.
  • the pharmacokinetic profile is characterized by a peak of maximum plasma concentration (C max ) which is reached within a rather short period of time (t max : approximately 1 hour) and by a rapid elimination (t ⁇ : approximately 3-4 hours) (Neugebauer G, Besenfelder E and Mollendorf E. Pharmacokinetics and metabolism of torasemide in man. Arzneim Forsch . /Drug Res . 1988;38 (1) : 164-166) .
  • Torasemide shows a, linear dose-response relationship at doses, from 2.5 to 20 mg for urinary volume.
  • An object of the present invention is to prepare diuretic compositions that may provide more stable plasma levels of torasemide in order to avoid the initial peak. This will provide a kinetic profile with fewer fluctuations and steadier levels. Thus, the frequency of urinary urgencies is reduced, which results in a greater comfort for patients who need treatment with torasemide.
  • compositions of the present invention comprise torasemide, as active ingredient, and an excipient chosen from matrix-forming polymers, for example, polymers of acrylic acid, cellulose, glycerol behenate, guar gum, xanthan gum, chitosan, gelatin, polyvinyl alcohol and the like.
  • matrix-forming polymers for example, polymers of acrylic acid, cellulose, glycerol behenate, guar gum, xanthan gum, chitosan, gelatin, polyvinyl alcohol and the like.
  • matrix-forming polymers for example, polymers of acrylic acid, cellulose, glycerol behenate, guar gum, xanthan gum, chitosan, gelatin, polyvinyl alcohol and the like.
  • compositions of the present invention are the usual excipients in pharmaceutical technology comprising diluents, for example, lactose, cellulose, mannitol, calcium phosphate and the like, as well as the mixtures thereof; binding- and disintegrating-action agents, for example, Aerosil ® 200, starch, and the like, as well as the mixtures thereof; lubricants, for example, magnesium stearate, talc, and the like, as well as the mixtures thereof.
  • the compositions of the present invention contain the active ingredient in a proportion from 0.5 to 20%, and the matrix-forming polymer in a proportion from 1 to 40%.
  • compositions of the present invention are tablets for oral administration.
  • compositions of the present invention maintain diuresis over a maximal period of 24 hours, preferably within the first 12 hours; thus, the possible disturbance of nocturnal enuresis is avoided. As the C max of plasma levels attained after administration is minimal, the troublesome urinary urgency induced by immediate-release compositions is prevented.
  • the tablets of the present invention contain the active ingredient, torasemide, in an amount of 0.5 to 20 mg. In practice, doses of 5, 10 and 20 mg per tablet are preferred.
  • the matrix-forming polymers are chosen from the following groups: 1) acrylic polymers, for example,
  • Carbopol ® (a carbomer -a polymer of acrylic acid polymer) , Kollicoat ® (a copolymer of methacrylic acid) , and their analogues and derivatives; 2) cellulose polymers, for example Methocel ® (hydroxypropylmethylcellulose) , methylcellulose, sodium carboxymethylcellulose, Natrosol ®
  • Meyprogat ® guar gum
  • compositions of the present invention contain the active ingredient, torasemide, in a proportion from 0.5 to 20% and the matrix-forming polymer in a proportion from 1 to 40%.
  • the most convenient matrix-forming polymer was found to be guar gum, preferably in a proportion of 4%.
  • other matrix-forming polymers may be employed in the compositions; their proportions may be varied within a relatively wide range.
  • Carbopol ® is formulated at concentrations from 1 to 20%, preferably 10%, Methocel ® at concentrations from 1 to 50%, preferably 40%, Natrosol ® and Compritol ® at concentrations from 1 to 40%, preferably 20%, Kollicoat ® at concentrations from 1 to 40%, preferably 15% and Meyprogat ® at concentrations from 1 to 40%, preferably 4%.
  • the tablets of the present invention are manufactured according to standard procedures of pharmaceutical technology by direct compression or by wet granulation in such a way that moisture of the resulting dry granulate is lower than 10 %.
  • Fig. 1 shows torasemide release (cumulative values) and Fig. 2 shows torasemide release.
  • Example 1 5 mg tablets of torasemide with Carbopol ® and a total weight of 85 mg
  • Aerosil ® 200 0.5 mg Mannitol q.s. 85 mg
  • Example 2 5 mg tablets of torasemide with Methocel ® and a total weight of 100 mg
  • Example 3 5 mg tablets of torasemide with Natrosol ® and a total weight of 85 mg
  • Aerosil ® 200 0.5 mg
  • Example 4 5 mg tablets of torasemide with Compritol ® and a total weight of 100 mg
  • Example 5 10 mg tablets of torasemide with Kollicoat ® and a total weight of 85 mg
  • Example 6 5 mg tablets of torasemide with Meyprogat ® and a total weight of 100 mg
  • Aerosil ® 200 0.5 mg
  • Example 7 5 mg tablets of torasemide with Meyprogat ® and a total weight of 85 mg
  • Example 8 10 mg tablets of torasemide with Meyprogat ® and a total weight of 170 mg
  • Example 9 20 mg tablets of torasemide with Meyprogat ® and a total weight of 340 mg
  • Aerosil ® 200 1.70 mg

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  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Inorganic Chemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Prolonged-release diuretic compositions containing torasemide as active ingredient. The compositions of the invention are useful to be able to avoid the troublesome urinary urgencies caused by conventional immediate- release compositions.

Description

PROLONGED-RELEASE COMPOSITIONS COMPRISING TORASEMIDE AND A MATRIX- FORMING POLYMER
Field of the invention This invention relates to prolonged-release diuretic compositions containing torasemide as active ingredient.
Brief description of the drawings Figure 1 shows the curves of in-vitro release rate (cumulative values) of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8. Figure 2 shows the curves of in-vitro release rate of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8. Figure 3 shows the plasma concentration curves in man after administration of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8. Figure 4 shows the versus-time curves of the number of urinary urgencies in man after administration of torasemide comparatively for immediate-release (IR) tablets and prolonged-release (PR) tablets according to Example 8.
Background of the invention
Torasemide (US 4018929) is a potent diuretic with an extensive clinical use. Torasemide mainly acts by inhibiting sodium reabsorption in the ascending limb of Henle's loop (Puschett JB and Jordan LL. Mode of action of Torasemide in man. Progress in Pharmacology and Clinical Pharmacology. 1990; 8 (1) : 7-13) . Torasemide interferes with Na+2C1"K+ pump in the luminal cell membrane and blocks the basolateral chloride conductance (Greger R. Inhibition of active NaCl reabsortion in the thick ascending limb of the loop of Henle by torasemide. Arzneim Forsch . /Drug Res. 1988;38(1) :151-155) .
The bioavailability for torasemide is 80-90% after oral administration, the kinetics is linear and the elimination half-life is 3-4 hours. The pharmacokinetic profile is characterized by a peak of maximum plasma concentration (Cmax) which is reached within a rather short period of time (tmax: approximately 1 hour) and by a rapid elimination (t^: approximately 3-4 hours) (Neugebauer G, Besenfelder E and Mollendorf E. Pharmacokinetics and metabolism of torasemide in man. Arzneim Forsch . /Drug Res . 1988;38 (1) : 164-166) . Torasemide shows a, linear dose-response relationship at doses, from 2.5 to 20 mg for urinary volume. The sodium excretion exerts a minimal effect on potassium. (Scheen AJ. Dose- response curve of torasemide in healthy volunteers . Arzneim Forsch. /Drug Res. 1988;38 (1) :156-159; Barr H et al . Torasemide dose-proportionality of pharmacokinetics and pharmacodynamics . Progress in Pharmacology and Clinical Pharmacology. 1990; 8 (1) :29-37) . The maximal effects on urine and electrolytes excretions are observed at approximately 2 hours after oral administration (Lesne M. Comparison of the pharmacokinetics and pharmacodynamics of torasemide and furosemide in healthy volunteers. Ar.zi-e.im Forsch . /Drug Res . 1988;38 (1) :160- 163) . All these effects clinically become apparent as an acute diuresis and by episodes of urinary urgency and suprapubic discomfort (Lambe R, Kennedy O, Kenny M and Darragh A. Study of tolerance and diuretic properties of torasemide following oral or intravenous administration to healthy volunteers . Eur J Clin Pharmacol 1986;31(Suppl) :9-14) .
Therefore, the availability of torasemide compositions, which may avoid the troublesome urinary urgencies caused by conventional immediate-release compositions is of a great interest.
Summary of the invention
An object of the present invention is to prepare diuretic compositions that may provide more stable plasma levels of torasemide in order to avoid the initial peak. This will provide a kinetic profile with fewer fluctuations and steadier levels. Thus, the frequency of urinary urgencies is reduced, which results in a greater comfort for patients who need treatment with torasemide.
The compositions of the present invention comprise torasemide, as active ingredient, and an excipient chosen from matrix-forming polymers, for example, polymers of acrylic acid, cellulose, glycerol behenate, guar gum, xanthan gum, chitosan, gelatin, polyvinyl alcohol and the like. In each composition one only polymer or a mixture thereof may be used. Other components that complete the compositions of the present invention are the usual excipients in pharmaceutical technology comprising diluents, for example, lactose, cellulose, mannitol, calcium phosphate and the like, as well as the mixtures thereof; binding- and disintegrating-action agents, for example, Aerosil® 200, starch, and the like, as well as the mixtures thereof; lubricants, for example, magnesium stearate, talc, and the like, as well as the mixtures thereof. Generally, the compositions of the present invention contain the active ingredient in a proportion from 0.5 to 20%, and the matrix-forming polymer in a proportion from 1 to 40%.
The compositions of the present invention are tablets for oral administration.
The compositions of the present invention maintain diuresis over a maximal period of 24 hours, preferably within the first 12 hours; thus, the possible disturbance of nocturnal enuresis is avoided. As the Cmax of plasma levels attained after administration is minimal, the troublesome urinary urgency induced by immediate-release compositions is prevented.
Detailed description of the invention
The tablets of the present invention contain the active ingredient, torasemide, in an amount of 0.5 to 20 mg. In practice, doses of 5, 10 and 20 mg per tablet are preferred. The matrix-forming polymers are chosen from the following groups: 1) acrylic polymers, for example,
Carbopol® (a carbomer -a polymer of acrylic acid polymer) , Kollicoat® (a copolymer of methacrylic acid) , and their analogues and derivatives; 2) cellulose polymers, for example Methocel® (hydroxypropylmethylcellulose) , methylcellulose, sodium carboxymethylcellulose, Natrosol®
(hydroxyethylcellulose) and their analogues and derivatives; 3) Compritol® (glyceryl behenate) ; 4)
Meyprogat® (guar gum) and its analogues and derivatives;
5) xanthan gum; 6) chitosan; 7) gelatin; and 8) polyvinyl alcohol and its derivatives . The compositions of the present invention contain the active ingredient, torasemide, in a proportion from 0.5 to 20% and the matrix-forming polymer in a proportion from 1 to 40%. The most convenient matrix-forming polymer was found to be guar gum, preferably in a proportion of 4%. However, other matrix-forming polymers may be employed in the compositions; their proportions may be varied within a relatively wide range. Thus, Carbopol® is formulated at concentrations from 1 to 20%, preferably 10%, Methocel® at concentrations from 1 to 50%, preferably 40%, Natrosol® and Compritol® at concentrations from 1 to 40%, preferably 20%, Kollicoat® at concentrations from 1 to 40%, preferably 15% and Meyprogat® at concentrations from 1 to 40%, preferably 4%.
The tablets of the present invention are manufactured according to standard procedures of pharmaceutical technology by direct compression or by wet granulation in such a way that moisture of the resulting dry granulate is lower than 10 %.
An in vitro dissolution test is performed on the tablets of the present invention using apparatus 2/paddle stirring element (according to U.S. Pharmacopeia) at 50 rpm.
In order to obtain a dissolution profile that fully models the physiological conditions, the test is performed within the first 2 hours at pH 1 and thereafter at pH 6.8. The results obtained are presented in Figures 1 and 2. Fig. 1 shows torasemide release (cumulative values) and Fig. 2 shows torasemide release.
The present invention is further illustrated by - but not limited to - the following examples . Example 1 : 5 mg tablets of torasemide with Carbopol® and a total weight of 85 mg
Torasemide 5.0 mg
Carbopol 940® 10.0 mg
Lactose 48.0 mg
Magnesium stearate 0.3 mg
Aerosil® 200 0.5 mg Mannitol q.s. 85 mg
Example 2: 5 mg tablets of torasemide with Methocel® and a total weight of 100 mg
Torasemide 5.0 mg
Methocel K 15 M® 40.0 mg
Lactose 18.0 mg
Corn starch 36.2 mg
Pregelatinized starch 0.3 mg Aerosil® 200 0.5 mg
Example 3: 5 mg tablets of torasemide with Natrosol® and a total weight of 85 mg
Torasemide 5.0 mg
Natrosol HX® 20.0 mg
Magnesium stearate 0.3 mg
Aerosil® 200 0.5 mg
Microcrystalline cellulose q.s. 85 mg
Example 4: 5 mg tablets of torasemide with Compritol® and a total weight of 100 mg
Torasemide 5.0 mg Compritol 888® 20.0 mg
Lactose 38.0 mg
Corn starch 36.2 mg
Magnesium stearate 0.3 mg Talc 0.5 mg
Example 5: 10 mg tablets of torasemide with Kollicoat® and a total weight of 85 mg
Torasemide 10.0 mg
Kollicoat® SR 30 D 30.0 mg
Magnesium stearate 0.6 mg
Talc 1.0 mg
Calcium phosphate q.s. 85 mg
Example 6: 5 mg tablets of torasemide with Meyprogat® and a total weight of 100 mg
Torasemide 5.0 mg Meyprogat® 90 4.0 mg
Lactose 54.0 mg
Corn starch 36.2 mg
Magnesium stearate 0.3 mg
Aerosil® 200 0.5 mg
Example 7: 5 mg tablets of torasemide with Meyprogat® and a total weight of 85 mg
Torasemide 5.0 mg Meyprogat® 90 3.4 mg
Corn starch 30.77 mg
Aerosil® 200 0.42 mg
Magnesium stearate 0.25 mg
Lactose 45.16 mg Example 8: 10 mg tablets of torasemide with Meyprogat® and a total weight of 170 mg
Torasemide 10.0 mg Meyprogat® 90 6.8 mg
Corn starch 61.54 mg
Aerosil® 200 0.85 mg
Magnesium stearate 0.51 mg
Lactose 90.30 mg
Example 9: 20 mg tablets of torasemide with Meyprogat® and a total weight of 340 mg
Torasemide 20.0 mg Meyprogat® 90 13.6 mg
Corn starch 123.08 mg
Aerosil® 200 1.70 mg
Magnesium stearate 1.02 mg
Lactose 180.6 mg
Example 10 : Pharmacokinetics of torasemide in man
A randomized clinical trial was performed in a group of 10 healthy volunteers who were cross-administered with a 10 mg prolonged-release tablet of torasemide and a 10 mg immediate-release commercial tablet of torasemide (Sutril®, Novag, Spain) . There was 1-week interval between the administration of each tablet. The prolonged-release torasemide composition exhibited a lower peak of plasma levels (Cmax) attained less acutely (tmax) with steadier levels and fewer fluctuations (Fig. 3) . The prolonged- release composition produced a lesser frequency of acute diuresis episodes than the immediate-release composition (Fig. 4) . These data show that the compositions of torasemide in the present invention produce a lower peak of plasma levels and fewer fluctuations than the immediate-release composition. In addition, there is a shorter number of urinary urgency episodes after the prolonged-release torasemide composition.

Claims

1. Prolonged-release compositions containing torasemide as active ingredient and a matrix-forming polymer.
2. Prolonged-release compositions according to claim 1, wherein these compositions are tablets for oral administration.
3. Prolonged-release compositions according to claim 1 and 2, wherein the matrix-forming polymer is selected from the group of polymers consisting of acrylic acid, cellulose, glycerol behenate, guar gum, xanthan gum, chitosan, gelatin, polyvinyl alcohol and the like, and mixtures thereof.
4. Prolonged-release compositions according to claim 3, wherein the acrylic matrix-forming polymer is selected from the group consisting of acrylic acid polymers and the like, and derivatives and mixtures thereof .
5. Prolonged-release compositions according to claim 3, wherein the cellulose matrix-forming polymer is selected from the group consisting of hydroxypropylmethylcellulose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, and the like, and their pharmaceutically acceptable salts, and mixtures thereof.
Prolonged-release compositions according to claim 3, wherein the matrix-forming polymer is guar gum.
7. Prolonged-release compositions according to preceding claims, wherein torasemide is present in a proportion from 0.5 to 20%.
8. Prolonged-release compositions according to claim 7, wherein torasemide is present in a proportion from 4 to 10 %.
9. Prolonged-release compositions according to preceding claims, wherein the matrix-forming polymers are present in a proportion from 1 to 50 %.
10. Prolonged-release compositions according to claim 9, wherein the matrix-forming polymers are present in a proportion from 2 to 40%.
11. Prolonged-release compositions according to preceding claims comprising in addition one or more excipients selected from the group consisting of diluents, binders, disintegrants, lubricants, and the like.
12. Prolonged-release compositions according to claim 11, wherein, the diluents are selected from the group consisting of lactose, celluloses, mannitol, calcium phosphate, and the like, and the mixtures thereof.
13. Prolonged-release compositions according to claim 11, wherein, the binders are selected from the group consisting of Aerosil® 200, starch, and the like, and mixtures thereof.
14. Prolonged-release compositions according to claim 11, wherein, the disintegrants are selected from the group consisting of Aerosil® 200, starch, and the like, and mixtures thereof.
15. Prolonged-release compositions according to claim 11, wherein, the lubricants are selected from the group consisting of magnesium stearate, talc, and the like, and mixtures thereof.
PCT/EP2005/051340 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer WO2005092291A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
US10/594,004 US20080187585A1 (en) 2004-03-25 2005-03-23 Prolonged-Release Compositions Comprising Torasemide and a Matrix-Forming Polymer
KR1020067021596A KR101203763B1 (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide
CN2005800093895A CN1946379B (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer
ES05717133.2T ES2632354T3 (en) 2004-03-25 2005-03-23 Extended release compositions comprising torasemide and a matrix forming polymer
AU2005227095A AU2005227095B2 (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer
MXPA06010833A MXPA06010833A (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer.
JP2007504420A JP4871258B2 (en) 2004-03-25 2005-03-23 Prolonged-release composition comprising toracemide and a matrix-forming polymer
CA2562142A CA2562142C (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer
EP05717133.2A EP1732517B1 (en) 2004-03-25 2005-03-23 Prolonged-release compositions comprising torasemide and a matrix-forming polymer
BRPI0509165-9A BRPI0509165A (en) 2004-03-25 2005-03-23 prolonged release compositions comprising torasemide and a matrix forming polymer
NO20064834A NO336582B1 (en) 2004-03-25 2006-10-24 Extended release preparations including torasemide, a matrix forming polymer and lactose

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES200400740A ES2244324B1 (en) 2004-03-25 2004-03-25 DIURETIC COMPOSITIONS OF PROLONGED RELEASE.
ESP200400740 2004-03-25

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EP (1) EP1732517B1 (en)
JP (1) JP4871258B2 (en)
KR (1) KR101203763B1 (en)
CN (1) CN1946379B (en)
AR (1) AR048432A1 (en)
AU (1) AU2005227095B2 (en)
BR (1) BRPI0509165A (en)
CA (1) CA2562142C (en)
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PA (1) PA8627401A1 (en)
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PT (1) PT1732517T (en)
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EP3065718A4 (en) * 2013-10-06 2017-07-12 Sarfez Pharmaceuticals, Inc. Controlled-release formulations comprising torsemide

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10463622B2 (en) * 2013-10-06 2019-11-05 Sarfez Pharmaceuticals, Inc. Treatments and formulations comprising Torsemide
US10596119B1 (en) * 2018-11-08 2020-03-24 Sarfez Pharmaceuticals, Inc. Methods of treatment comprising torsemide
EP3031471A1 (en) * 2014-12-12 2016-06-15 Ceva Sante Animale Veterinary composition for the treatment of pulmonary edema associated with heart failure in domestic animals

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003035029A1 (en) * 2001-10-25 2003-05-01 Depomed, Inc. Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data
US20030118648A1 (en) * 2001-11-30 2003-06-26 Jane Hirsh Pharmaceutical composition for compressed annular tablet with molded triturate tablet for both intraoral and oral administration
US20030153608A1 (en) * 2000-03-17 2003-08-14 Markus Maegerlein Torasemide-containing pharmaceutical preparations

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3305935C2 (en) * 1983-02-21 1985-05-30 Medice Chem.-Pharm. Fabrik Pütter GmbH & Co KG, 5860 Iserlohn Potassium neutral saluretic with antihypertensive effect
DE3529529A1 (en) * 1985-08-17 1987-02-19 Boehringer Mannheim Gmbh METHOD FOR PRODUCING A STABLE MODIFICATION OF TORASEMIDE
GB8601204D0 (en) * 1986-01-18 1986-02-19 Boots Co Plc Therapeutic agents
JP3586471B2 (en) * 1991-06-25 2004-11-10 三菱ウェルファーマ株式会社 Torasemide-containing pharmaceutical composition
DE19637082A1 (en) * 1996-09-12 1998-03-19 Boehringer Mannheim Gmbh Rapidly disintegrating pellets
GB9816899D0 (en) * 1998-08-05 1998-09-30 Boots Co Plc Therapeutic agents
CZ2002404A3 (en) * 1999-08-11 2002-06-12 Teva Pharmaceutical Industries Ltd. Polymorphous forms of torsemide
HUP0600143A2 (en) * 2000-02-17 2006-10-28 Teva Pharma A stable pharmaceutical formulation comprising torsemide modification ii
US20030119882A1 (en) * 2001-10-22 2003-06-26 Markus Maegerlein Solid pharmaceutical composition containing torasemide
US20030152622A1 (en) * 2001-10-25 2003-08-14 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral diuretic
US20030104052A1 (en) * 2001-10-25 2003-06-05 Bret Berner Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
HRP20020124A2 (en) * 2002-02-11 2003-10-31 Pliva D D Sustained/controlled release solid formulation as a novel drug delivery system with reduced risk of dose dumping
AU2004299077A1 (en) * 2003-12-12 2005-06-30 Penwest Pharmaceuticals Co. Sustained release torsemide dosage forms

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030153608A1 (en) * 2000-03-17 2003-08-14 Markus Maegerlein Torasemide-containing pharmaceutical preparations
WO2003035029A1 (en) * 2001-10-25 2003-05-01 Depomed, Inc. Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data
US20030118648A1 (en) * 2001-11-30 2003-06-26 Jane Hirsh Pharmaceutical composition for compressed annular tablet with molded triturate tablet for both intraoral and oral administration

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1732517A1 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3065718A4 (en) * 2013-10-06 2017-07-12 Sarfez Pharmaceuticals, Inc. Controlled-release formulations comprising torsemide
US10154963B2 (en) 2013-10-06 2018-12-18 Sarfez Pharmaceuticals, Inc. Controlled-release formulations comprising Torsemide

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CA2562142C (en) 2012-06-05
EP1732517B1 (en) 2017-05-03
PT1732517T (en) 2017-08-03
AR048432A1 (en) 2006-04-26
TWI351957B (en) 2011-11-11
PE20060015A1 (en) 2006-02-02
NO20064834L (en) 2006-12-07
EP1732517A1 (en) 2006-12-20
RU2449778C1 (en) 2012-05-10
ES2244324A1 (en) 2005-12-01
UY28809A1 (en) 2005-07-29
US20080187585A1 (en) 2008-08-07
TW200531693A (en) 2005-10-01
PL1732517T3 (en) 2017-09-29
MXPA06010833A (en) 2006-12-15
PA8627401A1 (en) 2005-11-25
CN1946379B (en) 2012-05-16
BRPI0509165A (en) 2007-09-11
JP2007530510A (en) 2007-11-01
AU2005227095B2 (en) 2010-10-28
CA2562142A1 (en) 2005-10-06
CN1946379A (en) 2007-04-11
ES2632354T3 (en) 2017-09-12
RU2006137671A (en) 2008-04-27
JP4871258B2 (en) 2012-02-08
KR101203763B1 (en) 2012-11-23
AU2005227095A1 (en) 2005-10-06
NO336582B1 (en) 2015-09-28
KR20060130756A (en) 2006-12-19
ES2244324B1 (en) 2006-11-16

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